FTO MODULATING COMPOUNDS AND METHODS OF USE

摘要

The present invention relates to compounds which modulate the level or activity of polypeptides having Fe(II) and 2-oxoglutarate (2QG)-dependent oxygenase activity in a cell, tissue, or subject, exemplified by the Fat Mass and Obesity Associated protein (FTO). Aspects relate to N-(3,4-dihydroxy-5-aryl-2-furanyl)-sulfonamides, methods for their synthesis, and methods of using these compounds to modulate the activity of FTO in a cell-free sample, a cell-based assay, and in a subject. Aspects are also directed to compositions comprising compounds which modulate the activity of FTO, including pharmaceutically-acceptable compositions, and to methods of preventing, ameliorating, or treating FTO-mediated conditions or diseases in a subject, including stroke, epilepsy, depression, and degenerative central nervous system disorders such as Alzheimer's and Parkinson's disease. Other aspects elate to use of the compounds to ameliorate or treat conditions associated with metabolic disorders, such as diabetes and obesity.